Nystatin-A was compared with Amphotericin-B, AZT and foscarnet for their respective abilities to inhibit the replication of human immunodeficiency virus (HIV-1) in H9 cells. Nystatin-A and Amphotericin-B are polyene macrolide antibiotics. Foscarnet, a trisodium phosphonoformate and AZT are the inhibitors of reverse transcriptase (RT). HIV-1 infected H9 cells were cultured for seven days in the presence of all these drugs,at various concentrations and RT activity and p24 antigen production were quantitated. Untreated, HIV-1 infected H9 cells served as controls. Nystatin-A inhibited viral replication most effectively at 10 g/ml, a concentration that did not affect cell viability. Nystatin-A treatment inhibited RT activity by 95% and p24 production by 90%. These levels of inhibition were comparable to that mediated by Amphotericin B AZT and foscarnet. Western blot analysis of the HIV-infected H9 cells treated with these drugs did not detect any viral protein at the cellular level. These findings were further corroborated by indirect immunofluorescense studies using monoclonal anti-gp120 FITC-conjugated antibodies, and by polymerase chain reaction analysis using a 32P-labeled probe. These results suggest that Nystatin-A merits attention as an antiviral drug for the treatment of HIV-1 infection. In-vivo drug delivery by liposome encapsulation is currently under study. Cerulenin, an inhibitor of fatty acid and sterol synthesis , has been shown to inhibit the HIV replication in H9 cells by 50%. Cerulenin was highly toxic to cells even at 2 ug/ml concentration. The synthetic peptide analog of HIV- protease, SKF-108922 was also shown to have an inhibitory effect on HIV- replication. Both of these agents will be incorporated in to immunoliposomes and future experiments will focus on delivering these agents with greater specificity to reduce toxicity. Haldol, (haloperidol) a closely related compound and known antipsychotic agent, was chosen for testing. Haloperidol inhibits the HIV-1 and HIV-2 proteases in a concentration dependent manner.